Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis
Background This study investigated the effect of short-chain fatty acids (SCFAs) on diabetes in a mouse model. Methods Autophagy in Akita mice and streptozocin (STZ)-induced diabetic C57BL/6 mice was determined by Western blots and immunohistochemistry (IHC). Western blots, IHC, hematoxylin and eosi...
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| Format: | Article |
| Language: | English |
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Korean Endocrine Society
2022-06-01
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| Series: | Endocrinology and Metabolism |
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| Online Access: | http://www.e-enm.org/upload/pdf/enm-2021-1336.pdf |
| _version_ | 1811316377781272576 |
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| author | Xiaoying Ma Qiong Wang |
| author_facet | Xiaoying Ma Qiong Wang |
| author_sort | Xiaoying Ma |
| collection | DOAJ |
| description | Background This study investigated the effect of short-chain fatty acids (SCFAs) on diabetes in a mouse model. Methods Autophagy in Akita mice and streptozocin (STZ)-induced diabetic C57BL/6 mice was determined by Western blots and immunohistochemistry (IHC). Western blots, IHC, hematoxylin and eosin staining, Masson staining, periodic acid-Schiff staining, and picrosirius red staining were conducted to detect whether autophagy and renal function improved in Akita mice and STZ-induced diabetic C57BL/6 mice after treatment of SCFAs. Western blots, IHC, and chromatin immunoprecipitation were performed to determine whether SCFAs affected diabetic mice via the histone deacetylase (HDAC2)/unc-51 like autophagy activating kinase 1 (ULK1) axis. Diabetic mice with kidney-specific knockout of HDAC2 were constructed, and IHC, Masson staining, and Western blots were carried out to detect whether the deletion of endogenous HDAC2 contributed to the improvement of autophagy and renal fibrosis in diabetic mice. Results Reduced autophagy and severe fibrosis were observed in Akita mice and STZ-induced diabetic C57BL/6 mice. Increased autophagy and reduced renal cell fibrosis were found in SCFA-treated Akita diabetic mice and STZ-induced diabetic C57BL/6 mice. Diabetic mice treated with SCFAs had lower HDAC2 expression and more enriched binding of ULK1 promoter sequences to H3K27Ac. Endogenous knockout of HDAC2 caused enhanced autophagy and decreased renal fibrosis in diabetic mice treated with SCFAs. Conclusion SCFAs enhanced autophagy of renal tubular cells and attenuated renal fibrosis in diabetic mice through the HDAC2/ULK1 axis. |
| first_indexed | 2024-04-13T11:47:48Z |
| format | Article |
| id | doaj.art-f718b3c51ea74382a8bcf26811f41a62 |
| institution | Directory Open Access Journal |
| issn | 2093-596X 2093-5978 |
| language | English |
| last_indexed | 2024-04-13T11:47:48Z |
| publishDate | 2022-06-01 |
| publisher | Korean Endocrine Society |
| record_format | Article |
| series | Endocrinology and Metabolism |
| spelling | doaj.art-f718b3c51ea74382a8bcf26811f41a622022-12-22T02:48:08ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782022-06-0137343244310.3803/EnM.2021.13362296Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 AxisXiaoying Ma0Qiong Wang1 Department of Gastroenterology, Kidney Disease and Hemodialysis Center, Shaanxi Provincial People’s Hospital, Xi’an, China Department of Gastroenterology, Kidney Disease and Hemodialysis Center, Shaanxi Provincial People’s Hospital, Xi’an, ChinaBackground This study investigated the effect of short-chain fatty acids (SCFAs) on diabetes in a mouse model. Methods Autophagy in Akita mice and streptozocin (STZ)-induced diabetic C57BL/6 mice was determined by Western blots and immunohistochemistry (IHC). Western blots, IHC, hematoxylin and eosin staining, Masson staining, periodic acid-Schiff staining, and picrosirius red staining were conducted to detect whether autophagy and renal function improved in Akita mice and STZ-induced diabetic C57BL/6 mice after treatment of SCFAs. Western blots, IHC, and chromatin immunoprecipitation were performed to determine whether SCFAs affected diabetic mice via the histone deacetylase (HDAC2)/unc-51 like autophagy activating kinase 1 (ULK1) axis. Diabetic mice with kidney-specific knockout of HDAC2 were constructed, and IHC, Masson staining, and Western blots were carried out to detect whether the deletion of endogenous HDAC2 contributed to the improvement of autophagy and renal fibrosis in diabetic mice. Results Reduced autophagy and severe fibrosis were observed in Akita mice and STZ-induced diabetic C57BL/6 mice. Increased autophagy and reduced renal cell fibrosis were found in SCFA-treated Akita diabetic mice and STZ-induced diabetic C57BL/6 mice. Diabetic mice treated with SCFAs had lower HDAC2 expression and more enriched binding of ULK1 promoter sequences to H3K27Ac. Endogenous knockout of HDAC2 caused enhanced autophagy and decreased renal fibrosis in diabetic mice treated with SCFAs. Conclusion SCFAs enhanced autophagy of renal tubular cells and attenuated renal fibrosis in diabetic mice through the HDAC2/ULK1 axis.http://www.e-enm.org/upload/pdf/enm-2021-1336.pdfdiabetesdiabetic nephropathiesfatty acids, volatileautophagyrenal fibrosis |
| spellingShingle | Xiaoying Ma Qiong Wang Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis Endocrinology and Metabolism diabetes diabetic nephropathies fatty acids, volatile autophagy renal fibrosis |
| title | Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis |
| title_full | Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis |
| title_fullStr | Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis |
| title_full_unstemmed | Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis |
| title_short | Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis |
| title_sort | short chain fatty acids attenuate renal fibrosis and enhance autophagy of renal tubular cells in diabetic mice through the hdac2 ulk1 axis |
| topic | diabetes diabetic nephropathies fatty acids, volatile autophagy renal fibrosis |
| url | http://www.e-enm.org/upload/pdf/enm-2021-1336.pdf |
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